1. Field of the Invention
The present invention relates to a micro array manufacturing apparatus in which a large number of living body samples such as DNA fractions are arranged on substrates to thereby manufacture a living body sample micro array.
2. Description of the Related Art
At present, a technology is increasingly being developed which analyzes all genes of various living bodies efficiently. A DNA micro array is an array in which a large number of spots such as DNA fractions having a given base array are arranged on substrates such as slide glasses or silicones; and the DNA micro array is essential to the above analysis. Also, by detecting the variation of a gene using the DNA micro array, for innumerable gene-related diseases, medical treatment proper for individual patients can be performed.
In JP-Y-10-503841, there is disclosed an apparatus which is used to manufacture such micro array. In this apparatus, a test solution including DNA fractions is held in an open capillary passage formed between a pair of long and narrow members disposed spaced from each other, the leading end portions of the long and narrow members are lightly hammered at the given positions of the substrates to make the test solution to adhere onto the substrate, thereby forming solution spots on the substrates.
However, in the above-mentioned apparatus, the quantity of the test solution that can be held in the open capillary passage at a time is relatively small. Therefore, when manufacturing a large number of micro arrays at the same time, the test solution must be frequently replenished into the open capillary passage, which takes long time for manufacture of the micro arrays.
Also, in case where the quantity of the test solution is small, the test solution is easy to dry up and thus the viscosity of the test solution is easy to vary, which makes it difficult to form a large number of spots in a stable manner.
The present invention aims at eliminating the drawbacks found in the above-mentioned conventional micro array manufacturing apparatus. Accordingly, it is an object of the invention to provide a micro array manufacturing apparatus which can manufacture a micro array stably with high efficiency as well as can be manufactured at low costs.
It is another object of the invention to provide a micro array manufacturing apparatus which is able to manufacture a micro array stably with high efficiency.
In attaining the above object, according to a first aspect of the invention, there is provided a micro array manufacturing apparatus, comprising: a working table capable of arranging a plurality of substrates thereon; a solution storing portion for storing a solution including a living body sample; hold means for taking in said solution from the solution storing portion to form the spot of the solution on each of the substrates; moving means for supporting the hold means and moving it in directions where it approaches and part away from the substrates, thereby allowing the hold means to form the solution spot; and, delivery means for supporting the moving means and delivering it in an area including the working table and solution storing portion to thereby give it two-dimensional coordinates, wherein the hold means is made up of a solution storing portion for storing the solution and a needle insertable into the solution storing portion to allow the solution stored in the solution storing portion to adhere onto each of the substrates by a given quantity; the moving means includes a support portion to be delivered by the delivery means, a first movable member capable of mounting the solution storing portion thereon and mounted in such a manner that it can be moved with respect to the support portion in given directions where it approaches and parts away from the substrates, a second movable member capable of mounting the needle thereon and mounted in such a manner that it can be moved in the given directions with respect to the first movable member, and drive means for driving the second movable member; and the first movable member is driven in linking with the second movable member to be driven by the drive means.
In the first aspect of the invention, since the solution stored in the solution storing portion is allowed to adhere onto the substrate using the needle, a large quantity of solution can be stored in the solution storing portion. Even in case where spots are formed successively on a large number of substrates, there is eliminated the need to replenish the solution frequently, which makes it possible to shorten the micro array manufacturing time. Also, because a large quantity of solution can be stored in the solution storing portion, the dry-up of the solution can be restricted and variations in the viscosity of the solution can also be restricted, which makes it possible to form the spots stably for a long period of time.
Further, in the first aspect of the invention, the first movable member is driven in linking with the second movable member which is driven by the drive means. That is, the simultaneous upward and downward movement operations of the second movable member and first movable member (that is, the needle and solution storing member) as well as the upward and downward movement operation of only the second movable member (that is, the needle) after the first movable member (that is, the solution storing member) is stopped are carried out only by the single drive means. Due to this, when compared with a case in which these two operations are carried out by individual drive means, the drive source of the whole apparatus can be reduced in number and the number of parts involved with the drive source can be reduced, thereby being able to attain the reduced cost of the whole apparatus. Also, use of the single drive means can reduce the weight of the arraying head to be driven by the delivery means, which can simplify the structure the structure of the micro array manufacturing apparatus and can reduce the weight thereof. Therefore, it is possible to drive the arraying head at a high speed by the linear drive mechanisms, which makes it possible to shorten the manufacturing time of the micro array.
Also, according to a second aspect of the invention, there is provided a micro array manufacturing apparatus, comprising: a working table on which a plurality of substrates can be arranged; a solution storing portion for storing a solution including a living body sample; hold means for taking in the solution from the solution storing portion to form the spot of the solution on each of the substrates; moving means for supporting the hold means and moving it in directions where it approaches and part away from the substrates, thereby allowing the hold means to form the solution spot; and delivery means for supporting the moving means and delivering it in an area including the working table and the solution storing portion to thereby give it two-dimensional coordinates, wherein the hold means is made up of a solution storing portion for storing the solution and a needle insertable into the solution storing portion to allow the solution stored in the solution storing portion to drop down onto each of the substrates by a given quantity; and the moving means includes a base portion to be delivered by the delivery portion, a first movable member capable of mounting the solution storing portion thereon and mounted in such a manner that it can be moved with respect to the base portion in given directions where it approaches and parts away from the substrate, a first restrict member for restricting the movement of the first movable member in one direction with respect to the base portion, a second movable member capable of mounting the needle thereon and mounted in such a manner that it can be moved in the given directions with respect to the first movable member, a second restrict member for restricting the movement of the first movable member in the other direction opposite to the above-mentioned one direction with respect to the first movable member, and drive means for driving the second movable member.
In the second aspect of the invention, since the solution stored in the solution storing portion is allowed to adhere onto the substrates using the needle, a large quantity of solution can be stored and held in the solution storing portion. Even when the spots are formed successively on a large number of substrates, there is eliminated the need to replenish the solution frequently, which makes it possible to shorten the micro array manufacturing time. Also, because a large quantity of solution can be stored and held in the solution storing portion, the dry-up of the solution can be restricted and variations in the viscosity of the solution can be restricted, thereby being able to form the spots stably for a long period of time.
In the second aspect of the invention, the first movable member is driven in linking with the second movable member which is driven by the drive means. That is, the simultaneous upward and downward movement operations of the second movable member and first movable member (that is, the needle and solution storing member) as well as the upward and downward movement operation of only the second movable member (that is, the needle) after the first movable member (that is, the solution storing member) is stopped are carried out only by the single drive means. Due to this, when compared with a case in which these two operations are carried out by individual drive means, the drive source of the whole apparatus can be reduced in number and thus the number of parts involved with the drive source can be reduced, thereby being able to attain the reduced cost of the whole apparatus. Also, use of the single drive means can reduce the weight of the driven portion to be driven by the delivery means, which can simplify the structure the structure of the micro array manufacturing apparatus and can reduce the weight thereof. This can realize the high-speed driving of the driven portion by the linear drive mechanisms, so that the manufacturing time of the micro array can be shortened.
By the way, in order to facilitate the understanding of the invention, to the component elements of the micro array manufacturing apparatus of the invention, there have been added reference characters shown in the accompanying drawings while they are respectively put in parentheses. However, such expression does-not mean that the invention is limited to the illustrated embodiments of the invention.
According to a third aspect of the invention, there is provided a micro array manufacturing apparatus, comprising: a working table on which a plurality of substrates are arranged; a solution storing portion for storing a solution including a living body sample; hold means for taking in said solution from said solution storing portion to form the spot of said solution on each of said substrates; moving means for supporting said hold means and moving said hold means in directions where said hold means approaches and goes away from said substrates, thereby allowing said hold means to form said solution spot; and delivery means for supporting said moving means and delivering said moving means in an area including said working table and said solution storing portion to provide two-dimensional coordinates; wherein said hold means comprises a solution storing portion for storing said solution and a needle insertable into said solution storing portion to allow said solution stored in said solution storing portion to adhere onto each of said substrates by a given quantity.
In the third aspect of the invention, since the solution stored in the solution storing portion is allowed to adhere onto the substrate using the needle, a large quantity of solution can be stored in the solution storing portion. Even in case where spots are formed successively on a large number of substrates, there is eliminated the need to replenish the solution frequently, which makes it possible to shorten the micro array manufacturing time. Also, because a large quantity of solution can be stored in the solution storing portion, the dry-up of the solution can be restricted and variations in the viscosity of the solution can also be restricted, which makes it possible to form the spots stably for a long period of time.
According to a fourth aspect of the invention, in the micro array manufacturing apparatus of the third aspect, said solution storing portion includes a tapered interior space. In the fourth aspect of the invention, the solution storing portion includes a tapered interior space. In case where the interior space of the solution storing portion is formed in a tapered manner, the solution can be held positively and, at the same time, when the needle projects from the solution storing portion, the quantity of solution moving to the needle can be controlled properly.
According to a fifth aspect of the invention, in the micro array manufacturing apparatus of the third aspect, said needle includes a flat portion formed in said substrate side leading end portion thereof.
In the fifth aspect of the invention, in the leading end of the needle, there is formed a flat surface. Thanks to this, the deformation of the leading end portion of the needle when the leading end of the needle is contacted with the substrate can be restricted, which makes it possible to form a spot stably.
According to a sixth aspect of the invention, in the micro array manufacturing apparatus of the third aspect of the invention, said needle includes a slit for holding said solution therein.
In the sixth aspect of the invention, in the needle, there is formed a slit for holding the solution therein, which makes it possible to increase the quantity of solution that can be held.
According to a seventh aspect of the invention, in the micro array manufacturing apparatus of the third aspect of the invention, there is further provided washing means which pours a washing solution into said interior space of said solution storing portion to thereby wash said interior space of said solution storing portion.
In the seventh aspect of the invention, there is further included washing means for washing the interior space of the solution storing portion. This eliminates the possibility that the solution held by the solution storing portion in a certain step can remain within the solution storing portion until a next step. This can prevent different kinds of solutions from being mixed together.